Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19

Syed, Fahim; Li, Wei; Relich, Ryan F; Russell, Patrick M; Zhang, Shanxiang; Zimmerman, Michelle K; Yu, Qigui

Systemic vascular injury occurs in COVID-19 patients, yet the underlying mechanisms remain unknown. To clarify the role of inflammatory factors in COVID-19 vascular injury, we used a multiplex immunoassay to profile 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs). COVID-19 patients had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only one cytokine (MIF) was among these altered analytes, while the rest were chemokines/growth factors. Additionally, only MMP-1 and VEGF-A were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. We further studied MMP-1 enzymatic activity and multiple endothelial cell (EC) activation markers (soluble forms of CD146, ICAM-1, and VCAM-1) and found that they were highly dysregulated in COVID-19 patients. Thus, COVID-19 patients have a unique inflammatory profile, and excessive MMP-1 and hyperactivation of ECs are associated with the severity of COVID-19.